Breakthrough science: hypoxia-inducible factors, oxygen sensing, and disorders of hematopoiesis

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Abstract

Hypoxia-inducible factors (HIFs) were discovered as activators of erythropoietin gene transcription in response to reduced oxygen (O2) availability. O2-dependent hydroxylation of HIFs on proline and asparagine residues regulates protein stability and transcriptional activity, respectively. Mutations in genes encoding components of the O2-sensing pathway cause familial erythrocytosis. Several small-molecule inhibitors of HIF prolyl hydroxylases are currently in clinical trials as erythropoiesis-stimulating agents. HIFs are overexpressed in bone marrow neoplasms, and the development of HIF inhibitors may improve outcomes in these disorders.

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Semenza, G. L. (2022, April 21). Breakthrough science: hypoxia-inducible factors, oxygen sensing, and disorders of hematopoiesis. Blood. Elsevier B.V. https://doi.org/10.1182/blood.2021011043

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